A Randomised Trial of Preoperative Radiotherapy for Stage T3 Adenocarcinoma of Rectum

This is a multi-centre randomised trial comparing long course (LC) preoperative chemoradiation with short course (SC) preoperative radiotherapy for patients with localised T3 rectal cancer.

Sex

All

Minimum age

18 Years

Inclusion Criteria:

All of the following must apply:

* Pathologically documented and clinically resectable adenocarcinoma of the rectum.
* The patient must be considered by the surgeon to be suitable for a curative resection.
* The patient must be considered by the radiation oncologist to have no contraindication to pre-operative radiotherapy.
* Clinical T3 stage tumour on endorectal ultrasound or MRI. When endorectal ultrasound cannot be performed satisfactorily due to a technical reason, such as stenosis or proximity of the tumour, and MRI is not available, infiltration of perirectal fat on CT scan is also acceptable.
* Tumour with lower border within 12 cm from anal verge on rigid sigmoidoscopy.
* ECOG performance status 0, 1 or 2.
* Adequate bone marrow function with neutrophil count at least 1.5 x 109/L and platelet count at least 100 x 109/L.
* Adequate liver function with bilirubin and alanine aminotransferase (ALT) \<= 1.5 times the upper limit of normal.
* Adequate renal function with serum creatinine \<= 1.5 times the upper limit of normal.
* Accessibility for treatment and follow-up.
* Written informed consent.

Exclusion Criteria:

* None of the following must apply:
* Evidence of distant metastases.
* Recurrent rectal cancer.
* Unstable cardiac disease or clinically significant active infection.
* Other cancer in the last 5 years except treated non-melanoma skin cancer or carcinoma in situ of the cervix.
* Pregnant or lactating females or female patients of childbearing potential who have not been surgically sterilized or are without adequate contraceptive measures.
* Contraindication to insertion of a suitable indwelling venous catheter e.g. implantable central venous device (infuse-a-port), Hickman catheter or peripherally inserted central catheter.
* Prior pelvic or abdominal radiotherapy.

• BACKGROUNDKapiteijn E, Marijnen CA, Nagtegaal ID, Putter H, Steup WH, Wiggers T, Rutten HJ, Pahlman L, Glimelius B, van Krieken JH, Leer JW, van de Velde CJ; Dutch Colorectal Cancer Group. Preoperative radiotherapy combined with total mesorectal excision for resectable rectal cancer. N Engl J Med. 2001 Aug 30;345(9):638-46. doi: 10.1056/NEJMoa010580. PMID 11547717
• BACKGROUNDFolkesson J, Birgisson H, Pahlman L, Cedermark B, Glimelius B, Gunnarsson U. Swedish Rectal Cancer Trial: long lasting benefits from radiotherapy on survival and local recurrence rate. J Clin Oncol. 2005 Aug 20;23(24):5644-50. doi: 10.1200/JCO.2005.08.144. PMID 16110023
• BACKGROUNDNgan SY, Fisher R, Burmeister BH, Mackay J, Goldstein D, Kneebone A, Schache D, Joseph D, McKendrick J, Leong T, McClure B, Rischin D. Promising results of a cooperative group phase II trial of preoperative chemoradiation for locally advanced rectal cancer (TROG 9801). Dis Colon Rectum. 2005 Jul;48(7):1389-96. doi: 10.1007/s10350-005-0032-x. PMID 15906126
• DERIVEDAnsari N, Solomon MJ, Fisher RJ, Mackay J, Burmeister B, Ackland S, Heriot A, Joseph D, McLachlan SA, McClure B, Ngan SY. Acute Adverse Events and Postoperative Complications in a Randomized Trial of Preoperative Short-course Radiotherapy Versus Long-course Chemoradiotherapy for T3 Adenocarcinoma of the Rectum: Trans-Tasman Radiation Oncology Group Trial (TROG 01.04). Ann Surg. 2017 May;265(5):882-888. doi: 10.1097/SLA.0000000000001987. PMID 27631775
• DERIVEDNgan SY, Burmeister B, Fisher RJ, Solomon M, Goldstein D, Joseph D, Ackland SP, Schache D, McClure B, McLachlan SA, McKendrick J, Leong T, Hartopeanu C, Zalcberg J, Mackay J. Randomized trial of short-course radiotherapy versus long-course chemoradiation comparing rates of local recurrence in patients with T3 rectal cancer: Trans-Tasman Radiation Oncology Group trial 01.04. J Clin Oncol. 2012 Nov 1;30(31):3827-33. doi: 10.1200/JCO.2012.42.9597. Epub 2012 Sep 24. PMID 23008301